The goal of the proposed research is the characterization of the innervation to the anterior segment of the eye by histochemical and biochemical means, placing greatest emphasis in the following areas. We will describe the nerves containing a variety of biologically active peptides using immunohistochemical techniques. With these techniques and other selected methods, we plan to continue to search for other neurohumors as yet undescribed in the anterior segment, with emphasis on biologically active peptides and biogenic amines. Although most work will be performed in laboratory animals, the studies will be extended to human eyes, particularly for characterization of the peptidergic innervation. To identify precisely the origin of specific nerve types, proposed studies include evaluation of ocular tissues after selective denervation, careful analysis of all autonomic ganglia serving the eye, and examination of these ganglia after injection into the anterior chamber of tracers of retrograde axoplasmic transport. We also seek to define the interrelationship of the various neurohumors in the peripheral innervation of the eye. To seek evidence for the coexistence of neurohumors in the nerves to the anterior segment, neuro-anatomical studies are proposed that will combine several techniques such as immunohistochemistry and retrograde axonal transport. Biochemical isolation and characterization of selected neurohumors is proposed as an important complement to the immunohistochemical methodology. Through these studies we seek to define in comprehensive detail the innervation of the anterior segment of the eye. Through the coordination of anatomical, histochemical, and biochemical studies, information will be derived necessary to understand the neural control mechanisms governing ocular physiology. These studies likely will lead to an improved understanding of the pathophysiology of important ocular diseases, most notably glaucoma and certain forms of inflammation. Furthermore, because of the importance of neural mechanisms in ocular pharmacology, these studies may well lead to new drug therapies.